Administration of the 5-HT1B receptor agonist m-chlorophenylpiperazine (m-CPP) to rats produced dose-dependent decreases in the locomotor activity and food intake. The locomotor suppressant effect of m-CPP was inhibited by the serotonergic antagonist, metergoline, but not by phentolamine, propranolol, clonidine, or haloperidol. The locomotor and the food-intake suppressant effects of m-CPP were enhanced following long-term treatment with the tricyclic antidepressant imipramine. These findings are compatible with the development of functional supersensitivity of 5-HT1B receptors during long-term antidepressant drug treatment. In another study, the food-intake suppressant effect of m-CPP was potentiated following short-term lithium treatment, while long-term lithium treatment caused attenuation, thus suggesting development of functional subsensitivity of 5-HT1B receptors following long-term lithium treatment. The combination of these results indicates that various agents effective in different types of affective disorders exert a modulatory influence on serotonergic function in vivo. These results in animal model studies also help validate the use of m-CPP as an index of central serotonergic function in investigations in humans.